Combinatory Effect of Pequi Oil (Caryocar brasiliense)-Based Nanoemulsions Associated to Docetaxel and Anacardic Acid (Anacardium occidentale) in Triple-Negative Breast Cancer Cells In Vitro

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmaceutics Pub Date : 2024-09-05 DOI:10.3390/pharmaceutics16091170

Alicia Simalie Ombredane, Natália Ornelas Martins, Gabriela Mara Vieira de Souza, Victor Hugo Sousa Araujo, Ísis O. Szlachetka, Sebastião William da Silva, Márcia Cristina Oliveira da Rocha, Andressa Souza de Oliveira, Cleonice Andrade Holanda, Luiz Antonio Soares Romeiro, Elysa Beatriz de Oliveira Damas, Ricardo Bentes Azevedo, Graziella Anselmo Joanitti

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Abstract

Combination therapy integrated with nanotechnology offers a promising alternative for breast cancer treatment. The inclusion of pequi oil, anacardic acid (AA), and docetaxel (DTX) in a nanoemulsion can amplify the antitumor effects of each molecule while reducing adverse effects. Therefore, the study aims to develop pequi oil-based nanoemulsions (PeNE) containing DTX (PDTX) or AA (PAA) and to evaluate their cytotoxicity against triple-negative breast cancer cells (4T1) in vitro. The PeNE without and with AA (PAA) and DTX (PDTX) were prepared by sonication and characterized by ZetaSizer® and electronic transmission microscopy. Viability testing and combination index (CI) were determined by MTT and Chou-Talalay methods, respectively. Flow cytometry was employed to investigate the effects of the formulations on cell structures. PeNE, PDTX, and PAA showed hydrodynamic diameter < 200 nm and a polydispersity index (PdI) of 0.3. The association PDTX + PAA induced a greater decrease in cell viability (~70%, p < 0.0001) and additive effect (CI < 1). In parallel, an association of the DTX + AA molecules led to antagonism (CI > 1). Additionally, PDTX + PAA induced an expressive morphological change, a major change in lysosome membrane permeation and mitochondria membrane permeation, cell cycle blockage in G2/M, and phosphatidylserine exposure. The study highlights the successful use of pequi oil nanoemulsions as delivery systems for DTX and AA, which enhances their antitumor effects against breast cancer cells. This nanotechnological approach shows significant potential for the treatment of triple-negative breast cancer.

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基于贝基油（巴西莸）的纳米乳剂与多西他赛和金合欢酸（西洋苻酸）在体外三阴性乳腺癌细胞中的联合作用

结合纳米技术的联合疗法为乳腺癌治疗提供了一种前景广阔的选择。在纳米乳液中加入牡丹油、无患子酸（AA）和多西他赛（DTX）可以放大每种分子的抗肿瘤效果，同时减少不良反应。因此，本研究旨在开发含有 DTX（PDTX）或 AA（PAA）的枇杷油基纳米乳剂（PeNE），并在体外评估其对三阴性乳腺癌细胞（4T1）的细胞毒性。采用超声法制备了不含 AA（PAA）和 DTX（PDTX）的 PeNE，并通过 ZetaSizer® 和电子透射显微镜对其进行了表征。活力测试和组合指数（CI）分别采用 MTT 法和 Chou-Talalay 法测定。流式细胞术用于研究制剂对细胞结构的影响。PeNE、PDTX 和 PAA 的流体力学直径小于 200 nm，多分散指数（PdI）为 0.3。联合使用 PDTX + PAA 会导致细胞存活率大幅下降（约 70%，p < 0.0001），并产生叠加效应（CI < 1）。与此同时，DTX + AA 分子的结合会导致拮抗作用（CI > 1）。此外，PDTX + PAA 会诱发明显的形态变化、溶酶体膜渗透和线粒体膜渗透的重大变化、G2/M 细胞周期阻滞和磷脂酰丝氨酸暴露。这项研究突出表明，贝壳油纳米乳剂成功地用作了 DTX 和 AA 的递送系统，从而增强了它们对乳腺癌细胞的抗肿瘤作用。这种纳米技术方法显示出治疗三阴性乳腺癌的巨大潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmaceutics Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science

CiteScore

7.90

自引率

11.10%

发文量

2379

审稿时长

16.41 days

期刊介绍： Pharmaceutics (ISSN 1999-4923) is an open access journal which provides an advanced forum for the science and technology of pharmaceutics and biopharmaceutics. It publishes reviews, regular research papers, communications, and short notes. Covered topics include pharmacokinetics, toxicokinetics, pharmacodynamics, pharmacogenetics and pharmacogenomics, and pharmaceutical formulation. Our aim is to encourage scientists to publish their experimental and theoretical details in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.

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